Portal hypertension in NAFLD
11 Jan 2022
The role that portal hypertension plays in the development of complications of liver cirrhosis is well known. Several studies have shown that an increase in portal pressure above the level of clinical significance is evident in patients with non-alcoholic steatohepatitis (NASH) even in the pre-cirrhotic phases. In a study by Mendes et al. 6% of patients with NASH and non-significant hepatic fibrosis (F0-F2) had indirect signs of portal hypertension [Ref 1]. Furthermore, in a study by Rodrigues et al. conducted on liver biopsies of patients with clinically significant portal hypertension (hepatic venous pressure gradient –HVPG- >10 mmHg), in 16% of the samples there were no traces of significant fibrosis and in 21% of the samples with no significant fibrosis the degree of fibrosis was F0-F1 [Ref 2]. It is also important to underline that the measurement of HVPG (derived from the difference between wedged and free hepatic venous pressures) appears to be less accurate in patients with non-alcoholic fatty liver disease (NAFLD) than in patients with hepatic fibrosis from other etiologies [Ref 3]. This is probably due to the fact that wedged hepatic venous pressures are often underestimated in patients with NAFLD. However, despite the alleged reduced accuracy of measurement methods, several studies appear to confirm the presence of a varying degree of increase of portal pressure in these patients and tried to give an explanation for this phenomenon. One of the most discussed hypotheses is that of sinusoidal pressure. Liver sinusoidal endothelial cells regulate blood flow, and it is known how NAFLD leads to endothelial dysfunction through the loss of fenestration in the surface of these cells in response to excessive lipid exposure [Ref 4]. Moreover, early-stage steatohepatitis induced by high fat glucose-fructose diet in rats seems to be responsible for a switch in liver sinusoidal endothelial cells immune pathways, making them more prone to neoangiogenesis, activation of hepatic stellate cells and increased portal pressure [Ref 5].
These observations related to portal hypertension in patients with NAFLD have very important clinical aspects. First of all, it is important to consider the risk related to the presence of portal hypertension in NAFLD in order to prevent complications and effectively treat these patients. It is also equally important to consider the suboptimal accuracy of the methods currently in use for measuring HVPG in patients with NAFLD to hypothesize different strategies. In this sense, it is fundamental to develop new diagnostic tools that allow noninvasive monitoring of portal hypertension. Finally, there is a clear need to investigate the role of portal hypertension (both clinically significant and subclinical) as a possible prognostic predictor and as a possible fibrogenic factor, which contributes primarily to the development and worsening of the degree of fibrosis in patients with NAFLD [Ref 6]. These observations could also represent new therapeutic perspectives in a pathology that, at the moment, is still awaiting a specific therapy.
- Mendes FD, Suzuki A, Sanderson SO, Lindor KD, Angulo P. Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012;10(9):1028-33.e2.
- Rodrigues SG, Montani M, Guixé-Muntet S, De Gottardi A, Berzigotti A, Bosch J. Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis. Clin Gastroenterol Hepatol. 2019 Sep;17(10):2101-2109.e1.
- Sourianarayanane A, Talluri J, Humar A, McCullough AJ. Stage of fibrosis and portal pressure correlation in nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol 2017;29:516-523.
- Hammoutene A, Rautou PE. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J Hepatol 2019;70:1278-1291.
- Bravo M, Raurell I, Hide D, Fernandez-Iglesias A, Gil M, Barbera A, et al. Restoration of liver sinusoidal cell phenotypes by statins improves portal hypertension and histology in rats with NASH. Sci Rep 2019;9:20183.
- Baffy G, Bosch J. Overlooked subclinical portal hypertension in non-cirrhotic NAFLD: Is it real and how to measure it? J Hepatol. 2021 Oct 2:S0168-8278(21)02090-0.